Mechanism Of Intestinal Secretion Research Articles

Modulation of Intestinal Tight Junctions: A Novel Mechanism of Intestinal Secretion † 482

Zonula occludens toxin (Zot) is a novel toxin elaborated by Vibrio cholerae that modulates intestinal tight junctions. Aim of the study was to establish whether the permeabilizing effect of the toxin leads to intestinal secretion. Rabbit intestine was mounted in Ussing chambers and exposed to increasing concentrations of purified toxin. The tissues were also fixed, exposed to Zot, and then processed for fluorescence microscopy to determine the distribution of the toxin receptor within the intestine. Finally, purified toxin was simultaneously perfused in three distinct rabbit intestinal segments in vivo and water and electrolytes absorption measured. Zot induced a time- and dose-dependent decrease of rabbit intestinal tissue resistance in vitro, starting at a toxin concentration of 1.1×10-13M. When tested in vivo, the toxin induced a secretion of water and chloride and the passage of polyethylene glycole 4000 in the bloodstream. Both the in vitro and in vivo effects of the toxin were reversible, were observed only in the small intestine but not in the colon, and paralleled the distribution of the toxin receptor within the intestine. In conclusion, the intestinal secretion induced by Zot follows the opening of tight junctions caused by the toxin and may represent a novel mechanism of intestinal secretion.

OPENING INTESTINAL TIGHT JUNCTIONS: A NOVEL MECHANISM OF INTESTINAL SECRETION.

Zonula occludens toxin (Zot) is a novel toxin elaborated by Vibrio cholerae that modulates intestinal tight junctions. Aim of the study was to establish whether the permeabilizing effect of the toxin leads to intestinal secretion. Rabbit intestine was mounted in Ussing chambers and exposed to increasing concentrations of purified toxin. The tissues were also fixed, exposed to Zot, and then processed for fluorescence microscopy to determine the distribution of the toxin receptor within the intestine. Finally, purified toxin was simultaneously perfused in three distinct rabbit intestinal segments in vivo and water and electrolytes absorption measured. Zot induced a time- and dose-dependent decrease of rabbit intestinal tissue resistance in vitro starting at a toxin concentration of 1.1×10-13M. When tested in vivo, the toxin induced a jejunal secretion of water (18.2±3.8 vs -28.1±7.5 μl/min.cm, control period vs Zot-exposed period, respectively, p=0.003) and chloride (10.8±3.2 vs -2.53±0.06 μEq/min.cm, p=0.01). Similar changes were observed in the ileum (water 39.3±7.1 vs -18.7±4.8 μl/min.cm, p=0.003; chloride 9.6±1.2 vs -2.5±0.3 μEq/min.cm), but not in the colon (water 11.5.3±4.7 vs 17.5±5.0 μl/min.cm; chloride 6.0±1.3 vs 8.6±2.3 μEq/min.cm). The secretory effect of Zot in the small intestine was associated with an increased passage of polyethylene glycole 4000 in the bloodstream. Both the in vitro and in vivo effects of the toxin were reversible and paralleled the distribution of the toxin receptor within the intestine. In conclusion, the intestinal secretion induced by Zot follows the opening of tight junctions caused by the toxin and may represent a novel mechanism of intestinal secretion.

The enterotoxic effect of zonula occludens toxin on rabbit small intestine involves the paracellular pathway

BACKGROUND & AIMS: Zonula occludens toxin is a novel toxin elaborated by Vibrio cholerae that modulates intestinal tight junctions. The aim of this study was to establish whether the permeabilizing effect of the toxin leads to intestinal secretion.METHODS: Rabbit intestine was mounted in Ussing chambers and exposed to increasing concentrations of purified toxin. The tissues were also fixed, exposed to zonula occludens toxin, and processed for fluorescence microscopy to determine the distribution of the toxin receptor within the intestine. Then purified toxin was simultaneously perfused in three distinct rabbit intestinal segments in vivo, and water and electrolyte absorption were measured.RESULTS: Zonula occludens toxin induced a time- and dose- dependent decrease of tissue resistance starting at a toxin concentration of 1.1 x 10(-13) mol/L. When tested in vivo, the toxin induced a secretion of water and chloride and the passage of polyethylene glycol 4000 in the bloodstream. Both the in vitro and in vivo effects of the toxin were observed only in the small intestine but not in the colon and paralleled the distribution of the toxin receptor within the intestine.CONCLUSIONS: The intestinal secretion induced by zonula occludens toxin follows the opening of tight junctions caused by the toxin, possibly representing a novel mechanism of intestinal secretion.(Gastroenterology 1997 Mar;112(3):839-46)

Mechanism of intestinal secretion: effect of cyclic AMP on rabbit ileal crypt and villus cells.

Cyclic AMP-dependent secretagogues such as cholera toxin inhibit the coupled absorption of Na+ and Cl- and stimulate the secretion of HCO3- and Cl- in the ileum. Aside from Cl- secretion, little is known about the mechanism of these cyclic AMP-mediated effects. We therefore determined the effect of forskolin, an agent known to increase intracellular cyclic AMP by stimulation of adenylyl cyclase, on Na+/H+ and Cl-/HCO3- exchange in isolated crypt and villus cells from rabbit ileum. Forskolin increased cyclic AMP in the villus cells and decreased intracellular pH. The effect of forskolin on pH in villus cells was HCO3- independent, Na+ dependent, and amiloride sensitive. Further, the rate of recovery from an acid load was decreased by forskolin. These data suggest that increasing cyclic AMP inhibits Na+/H+ exchange in villus cells. In crypt cells also, forskolin increased cyclic AMP; however, forskolin increased intracellular pH in these cells. The effect of forskolin in crypt cells was also HCO3- independent, Na+ dependent, and amiloride sensitive. However, the rate of recovery from an acid load was increased by forskolin, the opposite effect of that seen in villus cells. These data suggest that increasing cyclic AMP in crypt cells stimulates Na+/H+ exchange. Inhibition of Na+/H+ exchange on the brush border membrane in villus cells would be expected to inhibit coupled NaCl absorption (which occurs by coupling of Na+/H+ and Cl-/HCO3- exchange). Stimulation of Na+/H+ exchange in crypt cells, present only on the basolateral membrane, alkalinizes the cell, which would be expected to stimulate HCO3- secretion by stimulating the Cl-/HCO3- exchanger on the brush border membrane. Thus, these results provide a mechanism for some of the previously unexplained in vivo and in vitro effects of cyclic AMP on ileal electrolyte transport.

Mechanism of intestinal secretion. Effect of serotonin on rabbit ileal crypt and villus cells.

To determine the mechanism of action of an intestinal secretagogue, serotonin, we have isolated crypt and villus cells and demonstrated Na:H and Cl:HCO3 exchange activity using the intracellular pH-sensitive fluorescent dye, 2,7-bis (carboxy-ethyl)-5,6-carboxy-fluorescein. Serotonin alkalinized both crypt and villus cells. Alkalinization in villus cells was HCO3 dependent and Na independent. In contrast, alkalinization in crypt cells was HCO3 independent and Na dependent. In villus cells, recovery from an alkaline load induced by Cl removal, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid or propionate pulse, known to occur via the Cl:HCO3 exchange, is inhibited by serotonin. In contrast, in crypt cells, recovery from an acid load induced by Na removal, amiloride and NH4Cl pulse, known to occur via Na:H exchange, is stimulated by serotonin. These data suggest that serotonin is inhibiting Cl:HCO3 exchange in villus cells and stimulating Na:H exchange in crypt cells. These effects of serotonin would be expected to inhibit coupled Na and Cl absorption by villus cells and stimulate HCO3 secretion by crypt cells in the intact ileum.

Mechanisms of Intestinal Secretion

Mechanisms of Intestinal Secretion

Mechanisms of Intestinal Secretion

Mechanisms of Intestinal Secretion

Mechanisms of intestinal secretion. Vol. 12, Kroc foundation Series: Edited by Henry J. Binder. 319 pp., $28.00 Alan R. Liss, Inc., New York, New York, 1979

Mechanisms of intestinal secretion. Vol. 12, Kroc foundation Series: Edited by Henry J. Binder. 319 pp., $28.00 Alan R. Liss, Inc., New York, New York, 1979

Mechanisms of Intestinal Secretion

Mechanisms of Intestinal Secretion

Book Review: Mechanisms of Intestinal Secretion

Book Review: Mechanisms of Intestinal Secretion

Trigger mechanisms of intestinal secretion

Trigger mechanisms of intestinal secretion

Reflex effect of hydrochloric acid on intestinal secretion

A conclusion was drawn on the local reflex mechanism of intestinal secretion in response to stimulation of the mucous membrane with a 0.25% hydrochloric acid solution. This conclusion was based on the inhibition of secretion in the isolated intestinal portion of a dog under the effect of anesthetics, hexamethonium and atropine.